Bioelectrical Impedance Analysis of Water Reduction in Lower-Limb Lymphedema by Lymphaticovenular Anastomosis.

BACKGROUND: Although lymphedema is fundamentally abnormal accumulation of excess water in the extracellular space, previous studies have evaluated the efficacy of physiological bypass surgery (lymphaticovenular anastomosis [LVA]) for lymphedema without measuring water volume. This study clarified the water reductive effect of LVA using bioelectrical impedance analysis (BIA). METHODS: The efficacy of LVA for unilateral lower-limb lymphedema was evaluated using BIA in a retrospective cohort. The water volume of affected and unaffected legs was measured using multifrequency BIA before and after LVA. Preoperative measurements were undertaken after compression therapy for at least 3 months. The follow-up period after LVA was a minimum of 6 months. RESULTS: Thirty consecutive patients with unilateral lower-limb lymphedema were enrolled. The mean water volume reduction of the affected leg by LVA (ΔLBW) was 0.86 L (standard deviation [SD]: 0.86, median: 0.65) with a mean number of 3.3 anastomoses (SD: 1.7). The mean reduction rate of edema was 45.1% (SD: 36.3). Multiple linear regression analysis revealed water volume difference between the affected and unaffected legs before LVA (excess LBW) as the strongest predictor of ΔLBW (R 2 = 0.759, p < 0.01; ß = 0.500, p < 0.01). CONCLUSION: The LVA reduces the volume of accumulated body water in lower-limb lymphedema. As excess LBW most strongly predicted the amount of water volume reduction by LVA, body water volume measurement by BIA before LVA might identify patients with low excess LBW not expected to benefit from LVA, regardless of apparent differences in limb circumference.

Prednisolone markedly reduced serum IgG4 levels along with the improvement of pituitary mass and anterior pituitary function in a patient with IgG4-related infundibulo-hypophysitis.

In 2011 a 76 year-old man with a medical history of diabetes, hypertension and autoimmune pancreatitis was admitted to our hospital because of anorexia, general malaise and repeated hypoglycemia. When he was 72 years old, he suffered from pancreatitis, and pancreas head tumor was operated. IgG4-related pancreatitis was diagnosed histopathologically. On admission anterior pituitary function test revealed impaired response of ACTH and cortisol to CRH, and no response of GH, TSH and gonadotropin to GHRH, TRH and LHRH, respectively. Baseline PRL level was elevated. Serum IgG and IgG4 levels were markedly elevated. Pituitary MRI showed significant enlargement of pituitary gland and stalk. Chest CT suggested IgG4-related lung disease. IgG4-related infundibulo-hypophysitis was diagnosed based on the above mentioned past history and results of present examinations. Twenty mg of hydrocortisone, followed by 20 mg of prednisolone (PSL) and 25 µg of levothyroxine markedly reduced serum IgG4 levels and ameliorated the symptom, the size of pituitary and stalk, and anterior pituitary function (TSH, GH and gonadotropin), although diabetes insipidus became apparent due to glucocorticoid administration. This is a typical case of IgG4-related hypophysitis in which PSL causes marked improvement of pituitary mass and pituitary function along with the reduction of serum IgG4 levels.

Stretching of Mechanoreceptors in Superior Tarsal Muscle Reflexively Contracts Slow-Twitch Fibers in Facial Expression Muscles: A Case Series.

Levator palpebrae superioris muscle (LPSM) and facial muscles comprise fast-twitch fibers (FTFs) and slow-twitch fibers (STFs) but lack muscle spindles required to contract STFs reflexively. Voluntary contractions and microsaccades of FTFs in LPSM stretch mechanoreceptors in superior tarsal muscle (STM) to induce phasic contractions of STFs in LPSM and frontalis muscle via mesencephalic trigeminal nucleus (MTN). They also induce prolonged contractions of STFs in bilateral frontalis and orbital orbicularis oculi muscles and physiological arousal via MTN and rostral locus coeruleus (LC). We hypothesized that stretching of mechanoreceptors in STM also induces prolonged contractions of STFs in other facial expression muscles (FEMs) via rostral LC. To verify this hypothesis, we reported a case series of abnormal contractions of FEMs due to aponeurosis disinsertion and disordered mechanoreceptor stretching. The first and second cases, which showed unilaterally and bilaterally sensitized mechanoreceptors, respectively, recorded increased prolonged contractions of ipsilateral and bilateral grimacing muscles, respectively. The third and fourth cases with asymmetrically and bilaterally desensitized mechanoreceptors experienced asymmetrically and bilaterally decreased prolonged contractions of grimacing and smiling muscles, respectively. Preoperatively and after surgery was performed to adjust mechanoreceptor stretching and reinsert aponeuroses into tarsi, we evaluated prolonged contractions of grimacing and smiling muscles during primary gazing and facial expression movements. Surgery satisfactorily cured abnormal prolonged contractions of grimacing and smiling muscles. Stretching of mechanoreceptors in STM by microsaccades or voluntary contractions of FTFs in LPSM might activate rostral LC via MTN, which tonically or phasically stimulates FEM motor neurons to reflexively contract their STFs, respectively.

Stretching of Putative Mechanoreceptors in the Inferior Tarsal Muscle Regulates Tonic and Clonic Reflex Contractions of Slow-Twitch Fibers in the Palpebral Orbicularis Oculi Muscle Causing Apraxia of Eyelid Opening: A Case Series.

The levator palpebrae superioris muscle (LPSM) and facial muscles comprise both fast-twitch fibers (FTFs) and slow-twitch fibers (STFs). Still, they lack the muscle spindles to induce reflex contractions of STFs. Because reflex contractions of STFs in the LPSM and frontalis muscle, which are the major eyelid opening muscles, are induced by stretching of mechanoreceptors in the superior tarsal muscle, those in the palpebral orbicularis oculi muscle (POOM), which is the major eyelid closing muscle, should not be induced by stretching of the same proprioceptors but instead induced by the proprioceptors in the vicinity of the POOM. Apraxia of eyelid opening (AEO) after eyelid closure might be caused by prolonged POOM contraction. Most patients with AEO tend to stretch the upper and lower eyelids by applying contact lenses and eyedrops to disinsert the aponeurosis and retractor from the tarsi. They taught us that pulling down or raising the lower eyelid decreased or increased involuntary contraction of the POOM, which relieved or worsened AEO, respectively. Then, they asked us to have the lower eyelid lowered and the upper eyelid raised surgically. Whenever the upper eyelid is opened by contractions of the LPSM with the global layer of superior rectus muscle (GLSRM), the lower eyelid is concomitantly opened by contractions of the global layer of inferior rectus muscle (GLIRM), which counteracts the contraction of the GLSRM to maintain the visual axis. We hypothesized that patients with retractor disinsertion raise the lower eyelid by eyelid closure to stretch putative mechanoreceptors in the inferior tarsal muscle (ITM), which induces prolonged tonic and clonic reflex contractions of STFs in the POOM, resulting in AEO. To retrospectively verify the hypothesis, we report five cases with AEO. In the first case, AEO was induced by tight eyelid closure but was prevented by pulling down the lower eyelid during eyelid closure. Surgery to reinsert retractors into the tarsi cured AEO. In the second case, the patient sustained both severe aponeurosis-disinserted blepharoptosis and AEO. In this patient, the first surgery to reinsert aponeuroses to the the tarsi cured AEO, but a tight eyelid closure induced prolonged POOM contraction. The second surgery conducted to reinsert the retractors to the tarsi cured AEO. In the third case, with the entire eyelid AEO, surgery done to reinsert the retractors to the tarsi almost cured the entire eyelid AEO. In the fourth case, an increased clonic contraction of the POOM on the right eyelid after a tight eyelid closure was relieved by 4% lidocaine instillation to anesthetize the ITM. In the fifth case, downgaze induced clonic reflex contraction of the right POOM because of the right retractor disinsertion. Thus, prolonged tonic and clonic reflex contractions of STFs in the POOM appeared to be regulated by enhanced stretching of putative mechanoreceptors in the ITM in patients with retractor disinsertion due to increased contractions and microsaccades of FTFs in the GLIRM. Because reflex contractions of STFs in the POOM by stretching of putative mechanoreceptors in the ITM might essentially attach the upper and lower eyelids to the globe, AEO might simply be the increased reflex contraction of the POOM.

Human protein factory for converting the transcriptome into an in vitro-expressed proteome,.

Appropriate resources and expression technology necessary for human proteomics on a whole-proteome scale are being developed. We prepared a foundation for simple and efficient production of human proteins using the versatile Gateway vector system. We generated 33,275 human Gateway entry clones for protein synthesis, developed mRNA expression protocols for them and improved the wheat germ cell-free protein synthesis system. We applied this protein expression system to the in vitro expression of 13,364 human proteins and assessed their biological activity in two functional categories. Of the 75 tested phosphatases, 58 (77%) showed biological activity. Several cytokines containing disulfide bonds were produced in an active form in a nonreducing wheat germ cell-free expression system. We also manufactured protein microarrays by direct printing of unpurified in vitro-synthesized proteins and demonstrated their utility. Our 'human protein factory' infrastructure includes the resources and expression technology for in vitro proteome research.

A case of colorectal cancer with double-activating epidermal growth factor receptor mutations.

We describe the case of a 72-year-old woman with locally advanced lung tumor mimicking primary lung cancer. She was diagnosed with rectal cancer at the age of 65 years and was initially treated with platinum-based chemotherapy and thoracic irradiation as a treatment for primary lung cancer. One year later, a thyroid tumor was detected in her right thyroid lobe and was confirmed to have metastasized from rectal cancer based on pathological findings. Therefore, we suspected that she had metachronous double cancers and treated her with conventional chemotherapy for colorectal cancer. However, new life-threatening multiple lung metastases appeared. We treated her with the drug erlotinib because additional genetic analysis against primary lung tumor revealed typical double-activating epidermal growth factor receptor mutations. Histological review by immunostaining concluded that the primary lung tumor was composed of metastatic tumors from rectal cancer. In addition, genetic analysis revealed that the primary rectal cancer contained nearly the same types of double-activating epidermal growth factor receptor mutations as were present in the lung tumor. This is the first report of a case of rectal adenocarcinoma with double-activating epidermal growth factor receptor mutations.

[A case of small cell lung cancer that presented with paraneoplastic syndrome].

A 65-year-old man had suffered from systemic erythema from November 2008 and had noticed gradually progressing weakness in the upper and lower limbs. He received medical treatment in another hospital but his symptoms did not improve. He was admitted to our hospital for treatment of diabetes in June 2009, and his chest X-ray images and CT scans showed a mass shadow in the right upper lobe with hilar and mediastinal lymphadenopathy. We performed bronchoscopy, and diagnosed small cell lung cancer (T2N2M1, stage IV). However, he had hand grip weakness and continuing upper and lower limb muscle weakness, and therefore electromyography was performed, which showed the presence of waxing in the right leg. Subsequently, a diagnosis of Lambert-Eaton myasthenic syndrome was made. As he also showed ataxia of the left lower extremity, we also diagnosed paraneoplastic cerebellar degeneration. We gave the patient chemotherapy consisting of carboplatin and etoposide which resulted in the disappearance of his waxing, and his grip strength and erythema immediately improved with regression of the tumor after 1 course of chemotherapy. We report a case of small cell lung cancer associated with Lambert-Eaton myasthenic syndrome, paraneoplastic cerebellar degeneration and erythema which presented as paraneoplastic syndrome, which improved with chemotherapy.

Non-thermal cytocidal effect of infrared irradiation on cultured cancer cells using specialized device.

As infrared penetrates the skin, thermal effects of infrared irradiation on cancer cells have been investigated in the field of hyperthermia. We evaluated non-thermal effects of infrared irradiation using a specialized device (1100-18000 nm with filtering of wavelengths between 1400 and 1500 nm and contact cooling) on cancer cells. In in vitro study, five kinds of cultured cancer cell lines (MCF7 breast cancer, HeLa uterine cervical cancer, NUGC-4 gastric cancer, B16F0 melanoma, and MDA-MB435 melanoma) were irradiated using the infrared device, and then the cell proliferation activity was evaluated by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay. Proliferation of all the cancer cell lines was significantly suppressed by infrared irradiation. Total infrared output appeared to be correlated with cell survival. Increased temperature during infrared irradiation appeared not to play a role in cell survival. The maximum temperature elevation in the wells after each shot in the 20 and 40 J/cm(2) culture was 3.8 degrees C and 6.9 degrees C, respectively. In addition, we have shown that infrared irradiation significantly inhibited the tumor growth of MCF7 breast cancer transplanted in severe combined immunodeficiency mice and MDA-MB435 melanoma transplanted in nude mice in vivo. Significant differences between control and irradiated groups were observed in tumor volume and frequencies of TUNEL-positive and Ki-67-positive cells. These results indicate that infrared, independent of thermal energy, can induce cell killing of cancer cells. As this infrared irradiation schedule reduces discomfort and side effects, reaches the deep subcutaneous tissues, and facilitates repeated irradiations, it may have potential as an application for treating various forms of cancer.

Differential long-term stimulation of type I versus type III collagen after infrared irradiation.

BACKGROUND: The dermis is composed primarily of type I (soft) and type III (rigid scar-like) collagen. Collagen degradation is considered the primary cause of skin aging. Studies have proved the efficacy of infrared irradiation on collagen stimulation but have not investigated the differential long-term effects of infrared irradiation on type I and type III collagen. OBJECTIVE: To determine differential long-term stimulation of type I and type III collagen after infrared (1,100-1,800 nm) irradiation. METHODS AND MATERIALS: In vivo rat tissue was irradiated using the infrared device. Histology samples were analyzed for type I and III collagen stimulation, visual changes from baseline, and treatment safety up to 90 days post-treatment. RESULTS: Infrared irradiation provided long-term stimulation of type I collagen and temporary stimulation of type III collagen. Treatment also created long-term smoothing of the epidermis, with no observed complications. CONCLUSIONS: Infrared irradiation provides safe, consistent, long-term stimulation of type I collagen but only short-term stimulation in the more rigid type III collagen. This is preferential for cosmetic patients looking for improvement in laxity and wrinkles while seeking smoother, more youthful skin.

Long-term evaluation of collagen and elastin following infrared (1100 to 1800 nm) irradiation.

BACKGROUND: Infrared irradiation stimulates collagen production, but histological differences in its long-term effects on type I versus type III collagen and elastin in human tissue are unclear. OBJECTIVE: To investigate the effects of infrared irradiation. METHODS AND MATERIALS: In vivo human tissues in sun-protected and sun-exposed areas were irradiated with infrared. Histological samples were analyzed, and visual changes were assessed up to 90 days post-treatment. RESULTS: Infrared irradiation provided long-term increases in collagen and elastin levels on post-irradiation days 30, 60 and 90 compared to controls. Significant increases in type I collagen persisted until 30 and 60 days, and in sun-protected and exposed skin biopsies, respectively. Significant increases in type III collagen and elastin persisted until 90 days in both sun-protected and sun-exposed skin biopsies. CONCLUSION: Infrared irradiation provides safe and effective long-term stimulation of collagen I and III and elastin, which is beneficial for improving skin laxity and wrinkles.

[Patient with autoimmune alveolar proteinosis who did not respond to GM-CSF inhalation therapy and underwent repeated whole-lung lavage].

A 63-year-old man visited our department due to dry cough in September 2005. Chest radiography showed an infiltrative shadow extending from the bilateral hila to the peripheral areas. Chest CT scanning revealed a crazy-paving appearance. Bronchoalveolar lavage and transbronchial lung biopsy confirmed alveolar proteinosis. In addition, based on the absence of an underlying disease and a high titer of anti-granulocyte-macrophage colony-stimulating factor (GM-CSF) antibody, a diagnosis of autoimmune alveolar proteinosis was made. His course was observed on an outpatient basis because of mild symptoms, but dyspnea on exertion gradually increased. In July 2007, GM-CSF inhalation therapy was initiated in another hospital, but no improvement was observed. In November of the same year, he underwent whole-lung lavage for one lung followed by that for the other at our department. The symptoms rapidly improved after the lavage but were aggravated again after 6 months. In May 2008, whole-lung lavage was performed again. There have been no reports of adults with autoimmune alveolar proteinosis who did not respond to GM-CSF inhalation therapy and who underwent whole-lung lavage twice. GM-CSF inhalation therapy for autoimmune alveolar proteinosis is a pathogenesis-based epoch-making therapy, but the response rate is about 60%. In patients with treatment-resistant autoimmune alveolar proteinosis showing repeated aggravation of symptoms, whole-lung lavage under general anesthesia is a reliable therapeutic method.

[Pleomorphic carcinoma of the lung with uncommon initial manifestation of intestinal perforation].

A 47-year-old woman suddenly developed abdominal pain and visited the emergency room of our hospital. Chest and abdominal CT scan revealed free air in the abdominal cavity and a bulky pulmonary tumor in the right middle lobe. The perforated sigmoid colon was removed in an emergency operation. Histological examination of the resected tissue revealed undifferentiated carcinoma, but the histological differentiation could not be determined. We used immunohistochemical staining to distinguish primary non-small cell lung cancer from colon cancer; the resected tumor was positive for TTF-1 and CK7, but negative for CK20. Therefore, by using immunohistochemical staining we could diagnose the tumor of the large intestine as metastasis from non-small cell lung cancer. After the operation, systemic chemotherapy with carboplatin and docetaxel was repeated, but the lung tumor did not regress and the patient died. Autopsy examination confirmed the histology of the lung tumor as pleomorphic carcinoma. Morphological characteristics and the immunohistochemical staining pattern of the pulmonary tumor were consistent with that of the colon tumor. In Japan, this is the first report in which the initial manifestation of lung cancer was perforation of the large intestine due to metastasis.

[Pulmonary carcinomatous lymphangiosis from recurrent breast cancer 10 years after resection of the primary tumor].

A 55-year-old woman had a history of left mastectomy due to early breast cancer in 1998. She had been suffering from dyspnea on effort and dry cough since August in 2007, and visited our hospital 6 months later because the symptoms had been becoming worse. She was hypoxic and her chest radiograph showed bilateral diffuse shadows, so she was hospitalized. The specimen of transbronchial lung biopsy showed undifferentiated adenocarcinoma cells in lymphatics identified by lymphatic endothelium antibody D2-40 stain, so we diagnosed carcinomatous lymphangiosis. It also revealed the cells staining positive for Cytokeratin 7, negative for Cytokeratin 20, and positive for both estrogen receptor and progesterone receptor. These features were identical to the immunohistological findings of the specimen from the previously resected breast cancer. Chemotherapy with docetaxel was effective and improved her respiratory condition and the chest radiograph. The immunohistological findings are useful for diagnosis and selection of cancer therapy. We cannot find any case reports of recurrence with carcinomatous lymphangiosis over 10 years after resection of breast cancer in Japan. We must keep in mind that some cancers relapse after a long disease-free interval.

Sjögren syndrome-related plasma cell disorder and multifocal nodular AL amyloidosis: clinical picture and pathological findings.

Background: Localized nodular deposits of AL amyloid are seen in different tissues/organs; however, the pathogenesis of this form of amyloidosis remains unclear. Recently, Sjögren syndrome combined with localized nodular AL amyloidosis has been noted. Here, we report Sjögren syndrome cases showing multifocal nodular AL amyloidosis and the followed benign course. Materials and methods: We investigated the clinical pictures and histopathological findings of three cases with both presence of Sjögren syndrome and localized nodular AL amyloidosis, paying a special attention to the distribution of amyloidoma. Results: All three cases were middle-aged females. In two of three cases localized deposits of AL amyloid preceded Sjögren syndrome. Amyloidoma was detected in scalp, eyelid, cheek, larynx, trachea, lung and breast, and around these amyloid-deposited lesions infiltration of plasma cells was seen. Pulmonary amyloidosis was consistently accompanied with parenchymal cystic lesions, but this amyloidosis did not produce any significant respiratory symptoms. Some of large pulmonary amyloidomas showed cavity formation and subsequent shrinkage. In two cases amyloid deposition was found on gastric mucosa. Two cases received small doses of oral prednisone, with no further appearance of amyloidoma. Conclusion: Sjögren syndrome-related plasma cell disorder may be responsible for the formation of this unique multifocal nodular AL amyloidosis.

[Treatment-refractory-dental-extraction-associated pyothorax involving infection by 2 species of oral originated bacteria requires surgical debridement by video assisted thoracoscopic surgery (VATS)].

Cases of septic pulmonary embolism (SPE) diagnosed clinically by CT after dental extraction rarely include verification of bacteria from the local infection site. We report the case of a 70-year-old man without background disease suffering severe pyothrax after dental extraction. We detected two species of oral bacteria from his pleural effusion. Treatment was so difficult that it required surgical debridement by video assisted thoracoscopic surgery (VATS), even after the appropriate administration of antibiotics. According to the American Heart Association (AHA) prophylaxis guidelines for preventing infective endocarditis indicate that it is uncommon to prescribe antibiotics to patients without background disease after dental extraction. No appropriate Japanese guidelines exist considering the prevention of SPE causing severe pyothorax as in our case. The hematogenous spread of bacteria such as SPE caused by sepsis after tooth extraction thus requires more attended careful consideration in clinical practice if patients are to be properly protected against potentially serious complications.

Facial reanimation by transposition of the masseter muscle combined with tensor fascia lata, using the zygomatic arch as a pulley.

We have created a new way of reanimating the face, involving transposition of the masseter muscle combined with tensor fascia lata, and using the zygomatic arch as a trochlea to reconstruct the inferior facial paralysis. We used it on five patients who had facial palsy after excision of malignant parotid tumours. The wide skin defect that exposed the masseter muscle after total parotidectomy was reconstructed with a free flap. This method differs from those of other methods of transposing the masseter muscle in that force is applied at an upper lateral angle. Our method provided dynamic raising of the upper lip, the corner of the mouth, and the nasolabial fold in four patients. We consider it to be useful, particularly for prompt surgical reconstruction of facial palsy after total parotidectomy with a wide defect in the skin of the cheek.

Correlation between projection of the ear, the inferior crus, and the antihelical body: analysis based on computed tomography.

We investigated the correlation between projection of the ear and the antihelical folding angle to clarify which portion of the antihelix should be corrected in reconstruction of prominent ears using computed tomograms of 15 ears in 11 patients with fractures of the facial bones. The angle of the scaphotriangular fossa indicating the superior crus, cymba conchae-triangular fossa angle indicating the inferior crus, and the scaphoconchal angle indicating the antihelical body were measured. There was no relation between the cranioauricular angle and the angle of the scaphotriangular fossa. However, there were significant relations between the cranioauricular angle and the cymba conchae-triangular fossa angle, and the cranioauricular and scaphoconchal angles, which suggests that emphasis should be placed on reconstruction of the inferior crus and antihelical body when prominent ears are being corrected.

Near-Infrared Irradiation Increases Length of Axial Pattern Flap Survival in Rats.

Objective: We previously reported that near-infrared irradiation nonthermally induces long-lasting vasodilation of the subdermal plexus by causing apoptosis of vascular smooth muscle cells. To clarify the possible application of near-infrared irradiation to prevent skin flap necrosis, we evaluated the length of axial pattern flap survival in rats by near-infrared irradiation. Methods: A bilaterally symmetric island skin flap was elevated under the panniculus carnosus on the rat dorsum. Half of the flap was subjected to near-infrared irradiation just before flap elevation with a device that simulates solar radiation, which has a specialized contact cooling apparatus to avoid thermal effects. The length of flap survival of the near-infrared irradiated side was measured 7 days after flap elevation and compared with the nonirradiated side. Results: The irradiated side showed elongation of flap survival compared with the nonirradiated side (73.3 ± 11.7 mm vs 67.3 ± 14.9 mm, respectively, P = .03). Conclusions: Near-infrared irradiation increases the survival length of axial pattern flaps in rats.

Blepharoplasty with aponeurotic fixation corrects asymmetry of the eyebrows caused by paralysis of the unilateral frontalis muscle in Orientals.

Paralysis of the frontalis muscle causes ipsilateral brow ptosis and contralateral hypermotility of the non-paralytic frontalis muscle in Oriental patients. In this paper, we describe an effective way of correcting such asymmetry by using blepharoplasty with aponeurotic fixation, and three case reports were presented. This procedure makes it possible to reduce the hypermotility of the non-paralytic frontalis muscle, and symmetry of the brows can be achieved easily with minimal brow lift. All three patients had symmetrical brows six months postoperatively. Although we think that brow ptosis may recur eventually, if symmetry is obtained as a result of minimal brow lift, we think that our method can delay recurrence.